DESCRIPTION (From the applicant's abstract): Previous work produced two novel findings. Reproductive behavior and gonadal steroids produce an influx of mast cells (MC) into the medial habenula (MH) which subsequently granulate. As the MC is an ancient part of the vertebrate limbic system, the interaction between MC and MH neurons is likely to have far-reaching effects on behavior or homeostasis. The present hypothesis is that MC participate in coordinating reproductive events. Aim I utilizes a pharmacological approach to explore this. Several categories of drugs affecting the release of pre- or newly-formed mediators will be delivered into the CSF and daily injections given to away birds. Mates will be monitored from pairing to weaning of quabs. A related hypothesis is that MC migration into the brain is self-regulatory. In Aim II, using a similar approach, drugs are administered before pairing and animals killed 4 h later. Brains are examined histologically using a MC marker and MC number and distribution quantified. Next, how do MC influence neural activity? Does the BBB become permeable such that the milieu of the MH is altered? Inravascular injection of fluorescent dyes are sued to estimate the extend of BBB disruption. MC secretions can also act directly on adjacent neurons. As MC are confined to a chemical-definable sub-nucleus, do those MH neurons project to a precise domain of the interpeduncular nucleus? Information from Aims III and IV is for pursuing physiological experiments. Immune system cell traffic through the CNS. how they do so and what regulates this behavior is key to understanding the interactive processes between these two networks. The MC is unique, being both a visitor in the CNS with the capacity to communicate directly with neurons. These have the potential for creating an inflammatory response within the CNS but do not. Our goal is to elucidate the regulatory mechanisms behind this phenomena and the role(s) that MC play in the normal brain.